1. Field of the Invention
The invention relates to parathyroid hormone preparations.
2. Brief Description of Related Art
Parathormone (parathyroid hormone), or PTH, a regulatory hormone of calcium homeostasis, stimulates a number of enzymes. Among them are ornithine decarboxylase and adenylate cyclase. The target organs for PTH are the kidneys, on the one hand, and the bones on the other hand. In the kidneys, the hormone promotes the resorption of calcium and in the bones PTH cooperates in the mobilization of calcium as well as inducing incorporation of calcium.
J. Cell. Biol., 24 (1966) 316-323 (I; Borle & Neumann) describes a growth-promoting effect of PTH on Hela cells in-vitro. Biochem. Biophys. Res. Comm., 66 (1975) 188-194 (2; Morgan et al.) describes such an effect on T-lymphocytes, and Biochem. Biophys. Res. Comm., 129 (1985) 918-925 (3; van der Plas et al.) on osteoblasts from chickens when the osteoblasts were kept in secondary culture. Endocrinology, 118 (1986) 2445-2449) (4; M. Donald et al.) describes such an effect on bone cells. Endocrinology, 110 (1982) 506-512 (5; Tam et al.) describes an increased rate of in-vivo bone growth after the administration of PTH. Endocro Japan, 27 (1980) 349-356 (6; Kawashima et al.) and Calcif. Tissue Int., 35 (1983) 526-532 (7; Burch & Lebovitz) describe a stimulation by PTH of the proliferation of chicken embryo cartilage organ cultures in-vitro and Calcifo Tissue Int., 38 (1986) 155-162 (8; Lewinson & Silbermann) in mouse embryo cartilage organ cultures. In each of the above-mentioned studies, there was used PTH or a PTH fragment that simultaneously resulted in a stimulation of adenylate cyclase in renal cortex membranes, so that, when using this substance as a material for promoting bone growth in-vivo, influence on renal function must also be taken into account.
It is also known that a deletion of chain moieties at the natural N-terminus, as is demonstrated by the PTH fragment hPTh(28-48), results in a PTH fragment which will not stimulate renal adenylate cyclase; see Adv. Protein Chemistry, 35 (1982) 323 ff. (9; Potts et al.). Accordingly, it was not to be expected that, upon a deletion of amino acid residues from the chain structure of PTH, that the mitogenic action would not also be lost.